Orphanet Nomenclature & Orphanet Nomenclature &

Knowledge management

Ana Rath, Marc Hanauer, Annie Olry, Montserrat Alfaro, Martin Ana Rath, Marc Hanauer, Annie Olry, Montserrat Alfaro, Martin

Arles, Charlotte Gueydan, Sylvie Maiella, Charlotte Rodwell

marc.hanauer@inserm.fr

5th International Summer School on Rare Disease and Orphan Drug Registries, September 18-22, 2017

Roma

Orphanet, since 1997

• Mission:

– collect

– integrate

– produce

Added-value data and information on RD

- manually curated,

- expert-reviewed, – produce

– disseminate

• Reference nomenclature, classification and ontology of RD

- expert-reviewed,

- re-usable

www.orpha.net

Literature survey

PubMed queries

…

AnnotationIndexationWriting

ExpertsPatients groupsProfessionals

Completeness

Coherence

Sources survey

Catalog of RD-related services

www.orpha.net

Providing information

Providing data

International, multilingual websiteIntended to a multi-stakeholders audience

2016

www.orpha.netMassive agregated data in a computer-friendly format

Orphanet website users around the world VS Orphadata users

Orphanet

Orphadata

www.orpha.net

Orphanet in the RD landscape

ClinVarMedGen

www.orpha.net

Orphanet International database for RD

www.orpha.net

Interoperability

Research

Registries/Cohorts

Care

Health Information

System (EHRs)

Orphanet central

nomenclature

HGNC

OMIM

ICD10/11

GenesGenes

Terminologies

www.orpha.net

HGNC

OMIM

UniProt

Reactome

Ensembl

Genatlas

IUPHAR

ICD10/11

UMLS

MedDRA

DisabilitiesDisabilitiesPhenotypesPhenotypes

SNOMED

Orphanet RD nomenclature

ORPHA number Preferred label Synonyms

ORPHA:93545 Renal or urinary tract malformation CAKUT

Congenital anomalies of kidney and urinary tract

• The only clinical terminology specific for rare diseases

• Unique, stable ORPHA number

Congenital anomalies of kidney and urinary tract

ORPHA:216 Neuronal ceroid lipofuscinosis NCL

ORPHA:586 Cystic fibrosis CF

Mucoviscidosis

ORPHA:355 Gaucher disease Acid beta-glucosidase deficiency

Glucocerebrosidase deficiency

ORPHA:77259 Gaucher disease type 1 Non-cerebral juvenile Gaucher disease

www.orpha.net

• Unique, stable ORPHA number

• Definitions

• 8 languages (En, Fr, Es, It, Nl, De, Pt, Pl)

• Peer-reviewed publications only (2 cases<RD<1/2000)

RD classification

Organized by medical specialties• How?

Improve information

Epidemiology and statistics studies• Why?

www.orpha.net

Majority of systemic disorders• Particularity

Multi-dimensional

Multi- classification

Multi-hierarchicalMulti-dimensional Multi-hierarchical

www.orpha.net

Logical structure

Group

Category: clinically heterogeneous

Clinical group: clinically homogeneousClinical group: clinically homogeneous

Disorder:

• Disease, clinical syndrome, malformation

syndrome, morphological anomaly, biological

anomaly, particular clinical situation

Subtype:

• Clinical, etiological, histopathological

www.orpha.net

• Every entity is meaningful

• Entities are disjointed

• Parts are added to form the wholes

• Transitivity applies at every level

Rare bone disease Rare genetic disease

Primary bone dysplasia

Rare genetic bone disease

Spondylodysplastic dysplasia

Achondrogenesis

Achondrogenesis type IA

Sulfation-related bone disease

Rare bone disease related to a commongene or pathway defect

Achondrogenesis type IB

Achondrogenesis type II

Hypochondrogenesis

Update process

DBs(OMIM,…)

Literaturesurvey

Usersissues

Decision

Disease committee

Verification of prevalence, database and classification

consistency

Orphanet DB verification, literature search, expert advice Qualify the demand

Creation

New entry + infoReject

Modification

Nomenclature Obsolescence Deprecation

Expert advice

Disease committee

Impact on the inventory New Orpha numbers, Status modification

Impact on the classificationNew hierarchy including new orpha numbers

consitency inter- and intra-classification

Interoperability

Research

Registries/Cohorts

Care

Health Information

System (EHRs)

Orphanet central

nomenclature

HGNC

OMIM

ICD10/11

GenesGenes

Terminologies

www.orpha.net

HGNC

OMIM

UniProt

Reactome

Ensembl

Genatlas

IUPHAR

ICD10/11

UMLS

MedDRA

DisabilitiesDisabilitiesPhenotypesPhenotypes

SNOMED

Mappings with other terminologies

Terminology mapped RD

OMIM Manually 4,390

ICD-10 Manually All

Snomed-CT Manually 3,800

GARD Semi-automatically 2,998

Qualifier

E exact mapping (the terms and the concepts are equivalent)

NTBT narrower term maps to a broader term

BTNT broader term maps to a narrower term

W incorrect mapping (two different concepts)

ND not yet decided/unable to decide

GARD Semi-automatically 2,998

UMLS Semi-automatically 2,885

MeSH Semi-automatically 1,763

MedDRA Semi-automatically 1,224

www.orpha.net

ICD10 codes only :

Specific code The term has its own code in the ICD10

Inclusion term The term is included under a ICD10 category and has not its own code

Index term The term is oncluded in ICD10 index and refers to one more general code

Attributed

codeThe term does not exist in ICD10 and a code was attributed by Orphanet

Orpha number Preferred label Synonyms Typology Status ICD-10 Definition/relationship

ORPHA:93545 Renal or urinary tract

malformation

CAKUT Category _ _ _

Congenital anomalies of kidney and

urinary tract

ORPHA:216 Neuronal ceroid lipofuscinosis NCL Clinical group _ E75.4 Yes

Coding perspective

ORPHA:216 Neuronal ceroid lipofuscinosis NCL Clinical group _ E75.4 Yes

ORPHA:586 Cystic fibrosis CF Disease _ E84.0 E84.1

E84.8 E84.9

Yes

Mucoviscidosis

ORPHA:355 Gaucher disease Acid beta-glucosidase deficiency Disease _ E75.2 Yes

Glucocerebrosidase deficiency

ORPHA:1245 BIDS syndrome Amish brittle hair syndrome Disease Deprecated _ moved to Trichothiodystrophy

Trichothiodystrophy type D

ORPHA:77259 Gaucher disease type 1 Non-cerebral juvenile Gaucher disease Subtype _ E75.2 yes

ORPHA:101042 Taussig-Bing syndrome Subtype Obsolete _ Refered to Double outlet right

ventricle with subpulmonary

ventricular septal defect

www.orpha.net

Orpha numbers used to be assigned to a patient within an information system

=

Orpha Code

HPO annotations of Orphanet Rare Disorders

Around 6,000 rare disorders HPO phenotypes

2787 RD 5008 HPO

57,635 57,635

annotations

Frequencies Diagnostic criteria

Obligate (100%) Pathognomonic sign

Very frequent (99-80%) Diagnostic criterion

Frequent (79-30%)

Occasional (29–5%)

Very rare (1-4%)

Absent 0%

2787 RD 5008 HPOannotationsannotations

www.orpha.net

Absent 0%

Annotated by

Orphanet

Disseminated

by Orphanet

and HPO

BioPortal EBI - OLS

www.orpha.netOrphadata

To know more about…

Orphanet process

www.orpha.net

• Integrating pieces of a puzzling knowledge

Knowledge

– Around the Orphanet nomenclature and classification

• Providing integrated, re-usable data

– Orphanet Rare Disease Ontology (ORDO)

• Promoting interoperability

disease gene

phenotypedisability

www.orpha.net

– Bridging health and research

• Networking and partnering

Orphanet Curation Platformhttp://curation.orphanet.org

www.orpha.net

What is the Orphanet Curation Platform?

• It is a community-driven curation platform for rare disorders based on

Orphanet’s scientific content.

• It is a pilot project being co-developped by Orphanet and the Garvan

Institute (Australia), with the support of the Orphanet Australia’s country

coordinator.

• Goals:

– Allow users to visually explore the Orphanet scientific data

www.orpha.net

– Enable contributing experts and the Orphanet team to connect in a more dynamic and

efficient manner

– Facilitate communication between the contributing experts and the Orphanet team in

order to maintain the Orphanet database with the most up-to-date information

Orphanet Curation Platform « Key Players »

www.orpha.net

Create an Account

www.orpha.net

Browsing the Classification

www.orpha.net

www.orpha.net

www.orpha.net

Discussing a Suggestion

www.orpha.net

1

2

Life Cycle of a Suggestion

Suggestion posted by a

contributor Suggestion is incorporated

into Orphanet database

Suggestion appears on

Orphanet website

openBeing reviewed by the Orphanet team

Not yet accessedby Orphanet team

Curated by the Orphanet team

Being reassessed by

new

All persons involved in

closed

into Orphanet database Orphanet website

www.orpha.net

openReopen

the Orphanet teamBeing reassessed by the Orphanet team

Discussion of suggestion

between Orphanet team

& expert

All persons involved in

discussion agree on content of

suggestion

Harmonising phenomics information for a better interoperability in the rare diseases field

www.orpha.net

THANK YOU FOR YOUR ATTENTION

Orphanet Nomenclature & Knowledge management.

www.orpha.net

THANK YOU FOR YOUR ATTENTION